A Study of XZB-0004 in Patients With Solid Tumors

Phase 1

Recruiting

• Conditions: NSCLC; Advanced Solid Tumor
• Interventions: Drug: XZB-0004

• Registration Number: NCT05772455
• Lead Sponsor: Xuanzhu Biopharmaceutical Co., Ltd.

Brief Summary

XZB-0004 is a novel and potent small molecule inhibitor of receptor tyrosine kinase AXL.

This is an open-label, multicentre phase I study of XZB-0004 in patients with solid tumors. Part 1 is a dose-escalation study to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic profile of XZB-0004, and then to identify a safe and pharmacologically active dose for evaluation in subsequent cohorts or clinical studies. Part 2 is a study to evaluate the efficacy and safety of XZB-0004 combined with Penpulimab in patients with NSCLC or advanced solid tumors.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-20
• Study First Submitted QC: 2023-03-05
• Study First Posted: 2023-03-16
• Study Start: 2023-03-24
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-28
• Primary Completion: 2025-06
• Study Completion: 2027-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 128

Inclusion Criteria

1. Patient has signed informed consent before any trial related activities.
2. Be 18 years of age or older and less than 75 years at the time of signing the informed consent.
3. Part 1: Have a histologically or cytologically confirmed diagnosis of a solid tumour malignancy; Part 2：Have a histologically or cytologically confirmed diagnosis of a NSCLC or solid tumour malignancy.
4. Have evaluable (for Part 1) or measurable (for Part 2) disease as the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
5. Have a performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
6. Have adequate organ function.
7. Have recovered to ≤ grade 1 or Meet the requirements of the study from the effects of any prior cancer therapy, except for alopecia; irreversible neuropathy should have recovered to ≤ grade 2.
8. Have a life expectancy greater than 3 months.
9. Eligible patients (male and female) who are fertile must agree to at least use a reliable contraceptive method with partner.
10. Willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria

1. Previous use of AXL inhibitors and immunotherapy was consistent with protocol requirements.
2. Received anti-tumor therapy such as chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy or other therapy within 4 weeks prior to the first dose of the investigational drug.
3. Received other unmarketed investigational drugs or treatments within 4 weeks or 5 times the elimination half-life prior to the first dose of the investigational drug.
4. Treatment with systemic glucocorticoids (prednisone > 10mg per day or equivalent) or other immunosuppressive agents within 14 days before the first dose of a trial drug.
5. Inability to swallow, intestinal obstruction or other factors that affect the taking and absorption of the drug.
6. Patient with heart function impaired or clinically significant heart disease.
7. Any condition or illness that, in the opinion of the Investigator, would interfere with the evaluation of the safety of the study drug.
8. History of immune deficiencies, including positive HIV antibody tests.
9. Patient is in the active stage of HBV or HCV.
10. History of solid organ transplant or bone marrow transplant.
11. Any other malignant tumor has been diagnosed within 5 years.
12. Has known Primary tumor of the central nervous system or central nervous system metastase.
13. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage were present within 4 weeks before the first dose of the trial drug.
14. Subjects with psychiatric disorders that may affect trial compliance.
15. history of Alcoholism or drug abuse.
16. Pregnant or breastfeeding.
17. The researchers considered that there were some cases that were not suitable for inclusion.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
XZB-0004	XZB-0004	-

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) (for Part 1a)	Up to 3 weeks	Determine MTD of XZB-0004
Recommended phase 2 dose (RP2D）(for Part 1a)	Up to 3 weeks	Determine RP2D of XZB-0004
Overall Response Rate (ORR) (for Part 1b)	Up to 2-3 years	Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Secondary Outcome Measures

Name	Time	Method
Pharmakinetic parameter - t½ (for Part 1a and Part 1b)	Up to 63 days	To determine t½ of XZB-0004
Pharmakinetic parameter - CL/F (for Part 1a and Part 1b)	Up to 63 days	To determine CL/F of XZB-0004
Pharmakinetic parameter - AUC0-t (for Part 1a and Part 1b)	Up to 63 days	To determine AUC0-t of XZB-0004
Overall Response Rate (ORR) (for Part 1a)	Up to 2-3 years	Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Pharmakinetic parameter - Tmax (for Part 1a and Part 1b)	Up to 63 days	To determine Tmax of XZB-0004
Pharmakinetic parameter - Vz/F (for Part 1a and Part 1b)	Up to 63 days	To determine Vz/F of XZB-0004
Overall survival (OS) (for Part 1a and Part 1b)	Up to 2-3 years	OS is the time from the date of first dose of XZB-0004 to death due to any cause.
Pharmakinetic parameter - Cmax (for Part 1a and Part 1b)	Up to 63 days	To determine Cmax of XZB-0004
Duration of response (DOR) (for Part 1a and Part 1b)	Up to 2-3 years	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
Pharmakinetic parameter - AUC0-∞ (for Part 1a and Part 1b)	Up to 63 days	To determine AUC0-∞ of XZB-0004
Progression free survival (PFS) (for Part 1a and Part 1b)	Up to 2-3 years	PFS is defined as the time from the date of first dose of XZB-0004 till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).
Disease control rate (DCR) (for Part 1a and Part 1b)	Up to 2-3 years	DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1.
Incidence and severity of adverse events (AEs)(for Part 1b)	Up to 2-3 years	An adverse event (AE) is any untoward medical occurrence or the deterioration of existing medical event in a clinical study subject administered an investigational drug, which does not necessarily have an unequivocal causal relationship with the investigational product.

Trial Locations

Locations (1)

Shanghai Pulmonary Hospital; 🇨🇳 Shanghai, Shanghai, China